Control and/or calibration sera or compositions referred to as control and/or calibration sera are usually used for monitoring accuracy and precision of an assay method and for the calibration of analyzers. These sera and compositions contain the parameter to be detected in known, exactly defined concentrations. A distinction is made between special control and/or calibration sera which are used to control and calibrate selected parameters or a certain limited, often related group of parameters and universal control and/or calibration sera used to control and calibrate, if possible, all conventional parameters using any of the methods that are commonly known in the practice.
In daily routine work, such products must fulfill the following requirements:
an exactly defined concentration of the measuring parameters must be maintained PA1 the concentrations must be within the range of medical relevance (normal or pathological) PA1 handling of the control and/or calibration sera must be easy PA1 the control and/or calibration sera must have an extended storage stability
Especially high demands are made on the handling and storage stability when these control and/or calibration sera are used on automated analyzers. To date, most control and/or calibration sera have been available as lyophilisates thus ensuring an acceptable stability until the sera are reconstituted. This method is, however, very cumbersome and requires the use of a reconstituting solution. Lyophilisates often tend to become turbid which may cause analytical errors since the results of numerous detection methods involve colorimetric evaluation. Another source of errors is incorrect pipetting of the reconstituting solution. Once reconstituted, the reference or calibration sera are stable for only a few hours at room temperature. They must, hence, be prepared fresh every day. To facilitate handling, it is therefore desirable to make avalailable a reference or calibration serum that does not require pretreatment by the operator of the analyzer.
U.S. Pat. No. 3,876,375 describes a liquid biological composition that is used as a reference serum in diagnostic analysis. 20-40% alkylene polyols having 2-5 C-atoms, such as ethylene glycol, propylene glycol, butylene glycol, pentane diol and glycerol are used to stabilize this composition. When polyols in such high concentrations are added, the control and/or calibration serum may become viscous which may lead to problems and inaccuracies during the pumping and pipetting steps of the automated analyzer. It is therefore not suitable to add alkylene polyols in high concentrations.
In the preparation of a liquid-stable control and/or calibration serum, the bilirubin substrate limits stability in most cases. The bilirubin concentration is determined when hyperbilirubinemia is diagnosed. As a lyophilisate, bilirubin is sufficiently stable whereas after reconstitution stability is reduced to only a few hours at room temperature or to appr. two weeks at -20.degree. C.
U.S. Pat. No. 4,344,864 describes how conjugated bilirubin is stabilized by adding a sulfhydryl compound and a chelating agent at a pH of 8.2-9.2 in blood serum. For the preparation of a universal control and/or calibration serum it is, however, advantageous to use as few additives as possible. A stabilizing agent for one parameter often interferes with the determination of other parameters. Reducing agents which contain SH-groups can interfere with the subsequent enzymatic reaction, for example.
It is, hence, an object to provide a liquid control and/or calibration serum which is suitable for multiple parameter determinations in clinical diagnostics and contains bilirubin in a stabilized form. The object is accomplished by the invention which is characterized in greater detail in the disclosure which follows. The object is essentially accomplished in that the control and/or calibration serum contains a liquid-stable bilirubin derivative.